Łęga Tomasz, Weiher Paulina, Obuchowski Michał, Nidzworski Dawid
Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland.
Department of Recombinant Vaccine, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland.
PLoS One. 2016 Nov 30;11(11):e0167225. doi: 10.1371/journal.pone.0167225. eCollection 2016.
Effective vaccination against influenza virus infection is a serious problem mainly due to antigenic variability of the virus. Among many of investigated antigens, the extracellular domain of the M2 protein (M2e) features high homology in all strains of influenza A viruses and antibodies against M2e and is protective in animal models; this makes it a potential candidate for generation of a universal influenza vaccine. However, due to the low immunogenicity of the M2e, formulation of a vaccine based on this antigen requires some modification to induce effective immune responses. In this work we evaluated the possible use of Bacillus subtilis spores as a carrier of the Influenza A M2e antigen in mucosal vaccination. A tandem repeat of 4 consensus sequences coding for human-avian-swine-human M2e (M2eH-A-S-H) peptide was fused to spore coat proteins and stably exposed on the spore surface, as demonstrated by the immunostaining of intact, recombinant spores. Oral immunization of mice with recombinant endospores carrying M2eH-A-S-H elicited specific antibody production without the addition of adjuvants. Bacillus subtilis endospores can serve as influenza antigen carriers. Recombinant spores constructed in this work showed low immunogenicity although were able to induce antibody production. The System of influenza antigen administration presented in this work is attractive mainly due to the omitting time-consuming and cost-intensive immunogen production and purification. Therefore modification should be made to increase the immunogenicity of the presented system.
有效预防流感病毒感染的疫苗接种是一个严峻的问题,主要原因是病毒的抗原变异性。在众多被研究的抗原中,M2蛋白的胞外域(M2e)在所有甲型流感病毒毒株中具有高度同源性,针对M2e的抗体在动物模型中具有保护作用;这使其成为通用流感疫苗的潜在候选者。然而,由于M2e的免疫原性较低,基于该抗原的疫苗配方需要进行一些改进以诱导有效的免疫反应。在这项工作中,我们评估了枯草芽孢杆菌孢子作为甲型流感M2e抗原载体用于黏膜疫苗接种的可能性。编码人-禽-猪-人M2e(M2eH-A-S-H)肽的4个共有序列的串联重复与芽孢衣蛋白融合,并稳定地暴露在孢子表面,完整的重组孢子的免疫染色证明了这一点。用携带M2eH-A-S-H的重组内生孢子对小鼠进行口服免疫,无需添加佐剂即可引发特异性抗体产生。枯草芽孢杆菌内生孢子可作为流感抗原载体。尽管本研究构建的重组孢子能够诱导抗体产生,但其免疫原性较低。本研究中提出的流感抗原给药系统具有吸引力,主要是因为省略了耗时且成本高昂的免疫原生产和纯化过程。因此,应进行改进以提高所提出系统的免疫原性。